Tetrodotoxin, a sodium-channel blocking agent, is an indispensable tool in neurophysiological research. The overall objectives of this project are to develop practical procedures for the synthesis of tetrodotoxin derivatives which will then be readily available for research on the nature of the sodium channel and the mechanism of nerve conduction. Fundamentally these derivatives will be tetrodotoxin analogs modified at C-11. They will be designed to serve as photoaffinity, spin, fluorescent, and radioactive labels. These derivatives may also be adapted for the synthesis of compounds to be used in developing an immunoassay for tetrodotoxin and also for derivatives that may serve as local anesthetics. We propose to do this by protecting the 4 and 9 hydroxy groups with anhydro formation. Finally, the 4,9-anhydro bridge will be hydrolyzed, liberating the original tetrodotoxin structure at the guanidine portion of the molecule but now having a stable substituent introduced at C-11. This work will include continued studies on a practical total synthesis of tetrodotoxin and on structure activity relationships.